TRANSFERRIN-BINDING PROTEIN COMPLEX IS THE RECEPTOR FOR TRANSFERRIN UPTAKE IN TRYPANOSOMA-BRUCEI
TRANSFERRIN-BINDING PROTEIN COMPLEX IS THE RECEPTOR FOR TRANSFERRIN UPTAKE IN TRYPANOSOMA-BRUCEI
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DOI：
10.1083/jcb.131.5.1173
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发表时间：
1995-12-01
影响因子：
7.8
通讯作者：
OVERATH, P
中科院分区：
文献类型：
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作者：
STEVERDING, D;STIERHOF, YD;OVERATH, P
在布氏锥虫中，位于多顺反子表达位点中的变体表面糖蛋白基因上游的两个基因ESAG 6和ESAG 7的产物形成糖基磷脂酰肌醇锚定的转铁蛋白结合蛋白（TFBP）复合物。凝胶过滤和膜结合实验表明，TFBP复合物是异二聚体的，并以高亲和力结合一个转铁蛋白分子（每个细胞2，300个结合位点;对于来自T.布氏菌株427和EATRO 1125储备液的ES1.3A的K-D = 131 nM）。具有负载铁或无铁配体的转铁蛋白-TFBP三元复合物在pH 5至8之间稳定。用来自抗TFBP抗体的Fab片段可以抑制90%的细胞转铁蛋白摄取。摄取后，TFBP复合物及其配体被引导至溶酶体，其中转铁蛋白被蛋白水解降解。当降解产物从细胞中释放时，铁仍然与细胞结合，TFBP复合物可能再循环到鞭毛口袋的膜上，这是该生物体中胞外和内吞作用的唯一位点。结论：TFBP复合物是T.通过与哺乳动物细胞中不同的机制感染布氏杆菌。
In Trypanosoma brucei, the products of two genes, ESAG 6 and ESAG 7, located upstream of the variant surface glycoprotein gene in a polycistronic expression site form a glycosylphosphatidylinositol-anchored transferrin-binding protein (TFBP) complex. It is shown by gel filtration and membrane-binding experiments that the TFBP complex is heterodimeric and binds one molecule of transferrin with high affinity (2,300 binding sites per cell; K-D = 2.1 nM for the dominant expression site from T. brucei strain 427 and K-D = 131 nM for ES1.3A of the EATRO 1125 stock). The ternary transferrin-TFBP complexes with iron-loaded or iron-free Ligand are stable between pH 5 and 8. Cellular transferrin uptake can be inhibited by 90% with Fab fragments from anti-TFBP antibodies. After uptake, the TFBP complex and its ligand are routed to lysosomes where transferrin is proteolytically degraded. While the degradation products are released from the cells, iron remains cell associated and the TFBP complex is probably recycled to the membrane of the flagellar pocket, the only site for exo- and endocytosis in this organism. It is concluded that the TFBP complex serves as the receptor for the uptake of transferrin in T. brucei by a mechanism distinct from that in mammalian cells.